Heightened interest in apoptosis research and the discovery of the phosphatidylserine binding properties of annexin V have stimulated developments in cell death detection technologies and annexin mediated cellular targeting.
Cancer is one of the most common causes of death, taking nearly 7 million lives each year worldwide. New cancer targeted therapies that make use of therapeutic antibodies or small molecules have made treatment more tumor specific and less toxic. Thus, targeted therapies involving anticancer drugs are vigorously being pursued with the following rationale.
Most small molecule drugs are distributed in large volumes when given intravenously. The result of such treatment is often a narrow therapeutic index due to a high level of toxicity in normal tissues. Increasing doses of chemotherapeutic agents to overcome resistance or increase efficacy most often results in toxic side effects, which generally limits the effectiveness of conventional anti-tumor agents.
Through linkage of the chemotherapeutic drug to a macromolecular carrier, such as an annexin protein, the volume of distribution of the free drug can be significantly reduced and the concentration of free drug can be directed toward and concentrated in the tumor or the tumor endothelium, resulting in a decrease in the amount and types of non-specific toxicities, and an increase in the amount of drug that can be effectively delivered to the tumor per dosed equivalent of the drug entity.